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A potential role of dietary factors on the risk of ovarian cancer (OVC) has been suggested by ecologic studies due to observed differences in international incidence rates ([1][1]). The contribution of dietary factors to the etiology of OVC has been suggested through the modulation of the endogenous

A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

Background Finite mixture models posit the existence of a latent categorical variable and can be used for probabilistic classification. The authors illustrate the use of mixture models for dietary pattern analysis. An advantage of this approach is taking classification uncertainty into account. Methods Participants were a random sample of women from the European Prospective Investigation into Cancer. Food consumption was measured using dietary questionnaires. Mixture models identified latent classes in food consumption data, which were interpreted as dietary patterns. Results Among various assumptions examined, models allowing the variance of foods to vary within and between classes fit better than alternatives assuming constant variance (the K-means method of cluster analysis also makes the latter assumption). An eight-class model was best fitting and five patterns validated well in a second random sample. Patterns with lower classification uncertainty tended to be better validated. One pattern showed low consumption of foods despite being associated with moderate body mass index. Conclusion Mixture modelling for dietary pattern analysis has advantages over both factor and cluster analysis. In contrast to these other methods, it is easy to estimate pattern prevalence, to describe patterns and to use patterns to predict disease taking classification uncertainty into account. Owing to substantial error in food consumptions, any analysis will usually find some patterns that cannot be well validated. While knowledge of classification uncertainty may aid pattern evaluation, any method will better identify patterns from food consumptions measured with less error. Mixture models may be useful to identify individuals who under-report food consumption.

OBJECTIVE: To identify combinations of food groups that explain as much variation in absolute intakes of 23 key nutrients and food components as possible within the country-specific populations of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: The analysis covered single 24-h dietary recalls (24-HDR) from 36,034 subjects (13,025 men and 23,009 women), aged 35-74 years, from all 10 countries participating in the EPIC study. In a set of 39 food groups, reduced rank regression (RRR) was used to identify those combinations (RRR factors) that explain the largest proportion of variation in intake of 23 key nutrients and food components, namely, proteins, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, sugars (sum of mono- and disaccharides), starch, fibre, alcohol, calcium, iron, potassium, phosphorus, magnesium, vitamin D, beta-carotene, retinol and vitamins E, B1, B2, B6, B12 and C (RRR responses). Analyses were performed at the country level and for all countries combined. RESULTS: In the country-specific analyses, the first RRR factor explained a considerable proportion of the total nutrient intake variation in all 10 countries (27.4-37.1%). The subsequent RRR factors were much less important in explaining the variation (

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet–cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15 351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6·0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2·00; 95 % CI 1·30, 3·09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

BACKGROUND: International multicentre studies on diet and cancer are relatively new in epidemiological research. They offer a series of challenging methodological issues for the evaluation of the association between dietary exposure and disease outcomes, which can both be quite heterogeneous across different geographical regions. This requires considerable work to standardize dietary measurements at the food and the nutrient levels. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a calibration study was set up to express individual dietary intakes according to the same reference scale. A linear regression calibration model was used to correct the association between diet and disease for measurement errors in dietary exposures. In the present work, we describe an approach for analysing the EPIC data, using as an example the evaluation of the association between fish intake and colorectal cancer incidence. RESULTS: Sex- and country-specific attenuation factors ranged from 0.083 to 0.784, with values overall higher for men compared with women. Hazard ratio estimates of colorectal cancer for a 10 g/day increase in fish intake were 0.97 [95% confidence interval (CI): 0.95-0.99] and 0.93 (0.88-0.98), before and after calibration, respectively. CONCLUSIONS: In a multicentre study, the diet/disease association can be evaluated by exploiting the whole variability of intake over the entire study. Calibration may reduce between-centre heterogeneity in the diet-disease relationship caused by differential impact of measurement errors across cohorts. Udgivelsesdato: 2008-Apr

For epidemiological studies, a simple semiquantitative FFQ was developed to assess the frequency of intake of food items demonstrated with graphically displayed portion sizes. As a validation study, a random sample of 393 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study completed 2 unannounced 24-h dietary recalls (24HDR) and the FFQ during 1 y. To calculate food and nutrient intakes, we compared the use of fitted portion sizes with the use of predefined portion sizes. Fitted portion sizes were calculated by summing food intakes over the 2 24HDR and dividing the sum by the frequency of intake reported in the FFQ for each FFQ food item, leading to similar mean intakes for FFQ and 24HDR. As predefined portion sizes, amounts that had been used in previous dietary assessments in EPIC-Potsdam were used. Mean intake of 12 food groups was 102% for men or women with fitted portion sizes and 79% for men and 95% for women with predefined portion sizes of intake measured with 2 24HDR. However, deattenuated, energy-adjusted correlation coefficients between FFQ and 24HDR were not better for 19 nutrients by the use of fitted portion sizes, with a mean correlation coefficient of 0.53 for men and 0.56 for women. Mean correlation coefficients for food groups also were similar for fitted and predefined portion sizes. Fitting portion sizes using recent reference data from a random sample of study participants improved the quantitative assessment of food and nutrient intake, but not ranking of study participants, compared with predefining portion sizes based on prior knowledge.

Background and Purpose— Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phophate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. Methods— Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0±1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. Results— Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. Conclusions— Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.

Background Previous studies have shown dose-dependent and time-dependent effects of cigarette smoking and smoking cessation on C-reactive protein (CRP) concentrations in men, but results were inconsistent for women. The aim of this study was to evaluate the dose-dependent and time-dependent association of smoking and smoking cessation with CRP concentrations in men and women using a novel comprehensive smoking index (CSI). Design Cross-sectional study of representative US survey data (National Health and Nutrition Examination Survey 1999-2002). Methods The CSI simultaneously accounts for intensity, duration and time since cessation of smoking. We analyzed data of 3505 men and 3896 women using sex-specific multiple linear regression models adjusting for other determinants of CRP concentrations, including age, race/ethnicity, body mass index, alcohol intake, diabetes, physical activity, oral hormone use among women, and history of coronary heart disease, stroke, chronic obstructive pulmonary disease and arthritis. Results A positive association of similar strength was found between smoking and CRP concentrations in both men and women who did not use exogenous oral hormones. Among women who used exogenous oral hormones, no association with smoking was found. In older men and women it took several years after smoking cessation for CRP concentrations to return to that of individuals who never smoked. Conclusion Smoking is associated with dose-dependent and time-dependent increases in CRP concentrations in both men and women. Furthermore, the effect of exogenous oral hormones on CRP concentrations in women is affected by smoking in a dose-dependent fashion. Eur J Cardiovasc Prev Rehabil14:694-700 © 2007 The European Society of Cardiology

OBJECTIVE—We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations. RESEARCH DESIGN AND METHODS—A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35–65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TÜF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score. RESULTS—Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118–983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were −0.56 in the TÜF and −0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TÜF and 0.75 in the MeSyBePo studies. CONCLUSIONS—The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.

Objective: Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR. Design: In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR). Results: Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR. Conclusions: The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.

Disease can be caused by different mechanisms. A possible causal model proposed by Rothman is a complete causal mechanism or a so-called "sufficient cause" consisting of a set of component causes that can be illustrated in a pie chart. However, this model does not allow finding out what sufficient causes produce the majority of cases. The authors' objective was to extend Rothman's work by quantifying the proportion of disease that can be attributed to a class of sufficient causes. The underlying idea was to consider all combinations of a given set of known risk factors and to assign each combination to a class of sufficient causes. This assignment makes it possible to evaluate a class of sufficient causes by the population attributable fraction of the corresponding combination of risk factors. The approach presented was applied to sufficient causes of myocardial infarction by use of data on participants recruited between 1994 and 1998 into the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. As a result, 51.8% of cases were attributed to only four different classes of sufficient causes. In conclusion, the statistical method described in the paper may be beneficial for quantifying the importance of different sufficient causes and for improving the efficiency of public health programs.

The aim of the study was to identify a dietary pattern predictive of subsequent annual weight change by using dietary composition information. Study subjects were 24,958 middle-aged men and women of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. To derive dietary patterns, we used the reduced rank regression method with 3 response variables presumed to affect weight change: fat density, carbohydrate density, and fiber density. Annual weight change was computed by fitting a linear regression line to each person's body weight data (baseline, and 2- and 4-y follow-up) and determining the slope. In linear regression models, the pattern score was related to annual weight change. We identified a food pattern of high consumption of whole-grain bread, fruits, fruit juices, grain flakes/cereals, and raw vegetables, and of low consumption of processed meat, butter, high-fat cheese, margarine, and meat to be predictive of subsequent weight change. Mean annual weight gain gradually decreased with increasing pattern score (P for trend < 0.0001), i.e., subjects scoring high for the pattern maintained their weight or gained significantly less weight over time compared with subjects with an opposite pattern. However, the prediction of annual weight change by the food pattern was significant only in nonobese subjects. In this study population, we identified a food pattern characterized by high-fiber and low-fat food choices that can help to maintain body weight or at least prevent excess body weight gain.

Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m2 increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m2 carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.

Analysis of dietary patterns is considered a useful approach to the examination of diet-disease associations. This study examined the risk of incident hypertension associated with dietary patterns in 8,552 women in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam Study. The baseline examination was carried out between 1994 and 1998. During 2-4 years of follow-up (through May 15, 2002), 123 incident hypertension cases were verified by medical records. Two exploratory dietary patterns, a "traditional cooking" pattern (meat, cooked vegetables, sauce, potatoes, and poultry) and a "fruits and vegetables" pattern (fruits, raw vegetables, and vegetable oil), were identified by exploratory factor analysis and confirmed by confirmatory factor analysis. Additionally, a hypothesis-oriented pattern based on the Dietary Approaches to Stop Hypertension (DASH) Study was defined (fruits, vegetables, and milk products). Patterns' associations with disease risk were estimated by Cox regression. While no significant associations were observed for the traditional cooking pattern or the fruits and vegetables pattern after adjustment for potential confounders, women in the third quartile of the DASH pattern were at lower risk than women in the lowest quartile (hazard rate ratio = 0.51, 95% confidence interval: 0.29, 0.89). These results suggest that this hypothesis-oriented pattern might play an important role in the risk of hypertension.

Purpose: To compare history of 22 different diseases reported during an in-person interview with that reported on a mailed self-administered questionnaire. Methods: 7841 participants of the European Prospective Investigation into Cancer (EPIC)-Potsdam study. The interview at baseline and the questionnaire at follow-up approximately 2 years later included identical questions about whether the participant had ever had a physician diagnosis of each disease. Incident diagnoses occurring in the interval between the interview and questionnaire were excluded from the analysis. Results: Agreement between self-report from the interview and from the questionnaire was highest (κ=0.83–0.88) for myocardial infarction, cancer and diabetes mellitus; it was lower (κ=0.68–0.77) for gout, hypertension, hay fever, asthma, osteoporosis, ulcer of the duodenum, thyroid disease, stroke, and kidney stones, and was lowest (κ=0.39–0.59) for chronic gastritis, ulcer of the stomach, cerebral ischemia, benign tumor, inflammatory bowel disease, angina pectoris, hyperlipidemia, rheumatism, colon polyps and skin disease. The poor agreement for less severe or more transient diseases was primarily a result of disease frequently being reported at the interview but not on the questionnaire. Conclusion: Self-administered questionnaires do not generate same information particularly for less severe or transient diseases as personal interviews. For these diseases, self-administered questionnaires are not recommended. Pilot studies that test validity will be necessary.

Objective: To evaluate the influence of recent weight changes (weight gain, loss and cycling) on subsequent weight changes. Design: Prospective cohort study with 2 y of follow-up. Data analysis with a polytomous logistic regression model. Subjects: A total of 18 001 non-smoking subjects, 6689 men and 11 312 women, from the general population. Measurements: Body height and weight measurements and interview data on lifestyle habits and medical history at baseline. For follow-up, self-administered questionnaires for assessment of body weight and incident diseases. Results: Recent changes in body weight, that is weight gain, weight loss and weight cycling, were significant predictors of subsequent weight changes in both men and women after controlling for age, baseline BMI and several lifestyle and behavioural characteristics as potential confounding factors. Weight cycling before baseline was the strongest predictor of subsequent large weight gain (≥2 kg) with an odds ratio (OR) of 4.84 (95% confidence interval (CI) 3.34–7.02) in men. In women, prior weight loss was the strongest predictor of subsequent large weight gain (OR 4.77; 95% CI 3.63–6.03), followed by weight cycling (OR 3.02; 95% CI 2.15–4.25). Conclusion: These data indicate the need for thorough weight history assessment to identify those who are most likely to gain weight. Effective weight control before the development of obesity or after intentional weight loss due to obesity should be a primary goal in the management of obesity.

BMC systems biology 8(1), 55 (2014). doi:10.1186/1752-0509-8-55, Published by BioMed Central, London

Small antibody fragments are more useful than full-size antibodies for achieving efficient biodistribution. As a first step towards the design of a clinically desirable antibody fragment, the crystallization of a human V(H) fragment has been achieved. The fragment was derived from the single-chain antibody scFvM12, which recognizes a cancer-specific hypoglycosylated form of mucin. The V(H) fragment was obtained by in-drop digestion of the scFvM12 with a low concentration of the broad-spectrum protease subtilisin Carlsberg. The crystal belongs to the monoclinic space group C2. The crystal diffracted to 1.8 A resolution when analysed at 100 K using a rotating-anode X-ray generator.

PLoS one 8(10), e77656 (2013). doi:10.1371/journal.pone.0077656, Published by PLoS [u.a.], Lawrence, Kan.

An incidence rate ratio (IRR) is a meaningful effect measure in epidemiology if it is adjusted for all important confounders. For evaluation of the impact of adjustment, adjusted IRRs should be compared with crude IRRs. The aim of this methodological study was to present a statistical approach for testing the equality of adjusted and crude IRRs and to derive a confidence interval for the ratio of the two IRRs. The method can be extended to compare two differently adjusted IRRs and, thus, to evaluate the effect of additional adjustment. The method runs immediately on existing software. To illustrate the application of this approach, the authors studied adjusted IRRs for two risk factors of type 2 diabetes using data from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study from 2005. The statistical method described may be helpful as an additional tool for analyzing epidemiologic cohort data and for interpreting results obtained from Cox regression models with adjustment for different covariates.

It remains unclear what long-term effects of substituting carbohydrates at the expense of protein or fat may have with regard to diabetes risk. Our objective was to evaluate carbohydrate intake in predicting type 2 diabetes using substitution models for fat and protein. We conducted a prospective cohort study of 9702 men and 15 365 women aged 35–65 years and free of diabetes at baseline (1994–8) who were followed for incident type 2 diabetes until 2005. Dietary intake of macronutrients was estimated with a validated FFQ. We estimated the relative risk (RR) using Cox proportional hazards analysis. During 176 117 person-years of follow-up we observed 844 incident cases of physician-confirmed type 2 diabetes. After adjustment for age, BMI, waist circumference, potential lifestyle and dietary confounders, substituting 5 % of energy intake from total, saturated, or monounsaturated fat with carbohydrates was not associated with diabetes risk. In contrast, substituting carbohydrates for protein or PUFA was inversely related to diabetes risk (RR for 5 % energy substitution of protein 0·77 (95 % CI 0·64, 0·91); RR for PUFA 0·83 (95 % CI 0·70, 0·98)). These associations appeared to be similar for men and women, but gained statistical significance only among men for protein (RR 0·78 (95 % CI 0·61, 0·99)). Restricted cubic spline regression did not indicate non-linearity of these associations (P for non-linearity in full cohort was 0·353 and 0·349). In conclusion, a higher carbohydrate intake at the expense of protein and PUFA might be associated with decreased diabetes risk.

Recently, a food pattern predictive for prospective weight change was identified within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. Given the possible impact of weight change on cardiovascular disease (CVD) risk, we examined the association between the above mentioned food pattern and risk of CVD. The analyzed food pattern was defined by a high consumption of whole-grain bread, fruits, fruit juices, grain flakes and/or cereals, and raw vegetables, and a low consumption of processed meat, butter, high-fat cheese, margarine, and meat other than poultry. The associations between quartiles of the food pattern score and CVD morbidity and mortality were examined in 26,238 subjects of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort using a Cox's Proportional Hazards model for competing risks. During 6.4 y of follow-up, 379 incident cases of CVD were identified, of which 68 were fatal events. The food pattern was not associated with risk of nonfatal CVD. After adjusting for cardiovascular risk factors, the hazard ratios for fatal CVD across increasing quartiles of the score were 1.00, 0.85, 0.31, and 0.47, respectively (P for trend = 0.016). The association of the food pattern with CVD risk differed between fatal and nonfatal events (P for difference = 0.05). These findings from a large German cohort indicate that a food pattern predicting prospective weight change may be associated with the risk of fatal CVD.

Background Prospective data on the importance of established risk factors for myocardial infarction in Germany are sparse. Design The population-based cohort study European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam with 159 incident cases of myocardial infarction (120 men, 39 women) occurring among 26 954 participants (10 463 men, 16 491 women) during an average follow-up time of 4.6 years. Methods We examined the classic, potentially modifiable risk factors smoking, hypertension, hyperlipidemia, diabetes mellitus, abdominal obesity, and sporting inactivity, both individually and in combination, by estimating their prevalence and their relative and population-attributable risks of incident myocardial infarction. Results After adjusting for age, sex, educational attainment, alcohol intake, and the respective other classic risk factors the relative risks of myocardial infarction were 3.18 for smoking [95% confidence interval (CI) 2.31, 4.38], 1.84 for hypertension (95% CI 1.27, 2.65), 1.81 for sporting inactivity (95% CI 1.04, 3.15), 1.64 for diabetes (95% CI 1.05, 2.56), 1.62 for abdominal obesity (95% CI 1.03, 2.56), and 1.15 for hyperlipidemia (95% CI 0.84, 1.59). Participants with four or all five significant risk factors had an approximately 11.5-fold higher risk of the coronary event than participants with none or one risk factor. Altogether, 84.3% of myocardial infarctions in the study population were attributable to the presence of the five risk factors smoking, hypertension, diabetes, sporting inactivity, and abdominal obesity. Conclusion The majority of myocardial infarctions in the EPIC-Potsdam cohort were explainable by potentially modifiable classic risk factors. Therefore, besides efforts to investigate novel coronary risk factors, the prevention of coronary disease should focus on strategies to reduce the prevalence of established risk factors.

C-reactive protein (CRP) was proposed as a stronger predictor of cardiovascular events than low-density lipoprotein cholesterol (LDL-C); however, these associations may differ between myocardial infarction (MI) and stroke. We compared statistically the associations of CRP and LDL-C levels with risk of MI versus stroke and examined to what extent consideration of CRP or LDL-C increases the population attributable fractions (PAFs) of MI and stroke beyond traditional risk factors among 27,548 subjects from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study in a case-cohort design. Among subjects without prior MI or stroke, 156 developed MI and 132 stroke during 6.0 years of follow-up. In adjusted competing risk analyses CRP was positively related to MI and stroke (P difference between endpoints = 0.55), whereas LDL-C was related to MI but not stroke (P difference between endpoints = 0.003). The PAF for smoking, diabetes, and hypertension combined was 0.76 for MI, and 0.58 for stroke. With additional consideration of CRP the PAFs were 0.80 and 0.68, while with addition of LDL-C the PAFs were 0.88 and 0.55. We conclude that CRP is equally strongly related to risk of MI and stroke, whereas LDL-C is related to risk of MI but not stroke. Consideration of LDL-C beyond smoking, diabetes and hypertension may increase the PAF of MI slightly more than CRP. In contrast, consideration of CRP but not of LDL-C may increase the PAF of stroke beyond these factors.

ObjectiveTo investigate the association of a posteriori dietary patterns with overall survival of older Europeans.Design and settingThis is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors.SubjectsIn total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis.ResultsAn increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5–23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany.ConclusionsGreater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the survival of the same EPIC-Elderly cohort.

Obesity is a well-established risk factor for type 2 diabetes (1–3). However, while several studies (4–10) suggest that anthropometric measurements that describe central fat distribution are superior in predicting type 2 diabetes compared with measurements of general adiposity, this issue remains controversial (11–14). The aim of this study was to compare different anthropometric measurements and derived estimates of body composition, in particular BMI, waist-to-height ratio, waist-to-hip ratio (WHR), metric index, and percentage body fat, in their ability to predict risk of type 2 diabetes in a large prospective cohort study of men and women. The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study includes 27,548 subjects, 16,644 women aged mainly 35–65 years and 10,904 men aged mainly 40–65 years, from the general population of Potsdam, Germany, recruited between 1994 and 1998 (15). The baseline examination included anthropometric measurements (16,17) as well as a personal interview and a questionnaire on prevalent diseases and sociodemographic and lifestyle characteristics. Follow-up questionnaires have been administered every 2–3 years. Response rates for follow-up rounds 1, 2, 3, and 4 were 96, 95, 91, and 90% (31 August 2005), respectively. All potential incident cases of diabetes were verified by the diagnosing physician using …

Dietary pattern analysis, which reflects the complexity of dietary intake, has received considerable attention by nutritional epidemiology. For a long time, two general approaches have been used to define these summary variables in observational studies. The exploratory approach is based only on the data of the study, whereas the hypothesis-oriented approach constructs pattern variables based on scientific evidence available before the study. Recently, a new statistical method, reduced rank regression, was applied to nutritional epidemiology that is exploratory by nature, but can use scientific evidence by focusing on disease-related dietary components or biomarkers. Several studies, both observational and clinical, suggest that dietary patterns may predict the risk of CHD and stroke. In the present review, we describe the results of these studies and the available evidence regarding the relationships between dietary patterns and risk of CVD and we discuss limitations and strengths of the statistical methods used toextract dietary patterns.

Single, modifiable risk factors for stroke have extensively been studied. In contrast, differences of their combined effects among stroke and transitoy ischemic attack (TIA) have been rarely investigated. The aim of the present study was to assess single and joint effects of risk factors on the incidence of stroke and TIA and to compare their magnitudes in a large population-based German cohort.Incident cases of stroke and TIA were identified among 25,538 participants (aged 35-65 at baseline) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Relative risks for stroke and TIA related to modifiable risk factors were estimated using Cox proportional hazard models.During 4.3 years of follow-up 100 stroke cases and 112 TIA cases occurred. Incidences of stroke and TIA were 91.7 and 102.7 per 100,000 person-years, respectively. Relative risks for ischemic stroke (RR 5.12, 95% CI 1.49-17.6, p for trend0.0001) and for TIA (RR 3.08, 95% CI 1.00-9.44, p for trend0.024) were highest among participants having 4 or 5 modifiable risk factors. 58.5% of ischemic strokes and 26.2% of TIA cases were attributable to the 5 risk factors hypertension, diabetes mellitus, high alcohol consumption, hyperlipidemia, and smoking.Our data indicate that classical risk factors may explain almost 60% of ischemic stroke but only one in four TIA cases. Analysing potential differences of known risk factors between ischemic stroke and TIAs and the identification of other determinants of ischemic attacks are important steps to better explain the burden of stroke.

Homozygosity for the interleukin-6 (IL-6) g.-174GC promoter polymorphism has recently been associated with indices of overweight. Homozygous subjects were observed to have reduced energy expenditure, suggesting that lower IL-6 gene transcription, caused by the IL-6 g.-174GC promoter polymorphism, may be associated with obesity. The aim of this study was to investigate the association of this polymorphism with long-term weight gain. For 334 normal weight (20BMIor = 25 kg/m2) and 334 obese (BMI30 kg/m2) subjects matched by age and sex originating from the population-based EPIC-Potsdam Study, recalled weight change from age 25 to study enrollment was determined, the IL-6 g.-174GC promoter polymorphism was defined, and plasma concentrations of IL-6 and C-reactive protein were measured. The IL-6 g.-174GC promoter polymorphism was significantly associated with obesity (chi2 = 7,34, p = 0.026). Odds ratios for subjects with GC and CC genotypes for obesity were 1.19 (95% CI: 0.84 to 1.68; p = 0.323) and 1.91 (95% CI: 1.19 to 3.08; p = 0.007), respectively. Recalled weight change from age 25 years to study enrollment differed significantly according to genotype (p = 0.044) and was most pronounced in subjects with the CC genotype, suggesting that the IL-6 g.-174GC promoter polymorphism is a susceptibility or modifying locus for common obesity and weight gain.

Contains fulltext : 49468.pdf (Publisher’s version ) (Closed access) Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (

Dietary patterns are comprehensive variables of dietary intake appropriate to model the complex exposure in nutritional research. The objectives of this study were to identify dietary patterns by applying two statistical methods, principal component analysis (PCA) and reduced rank regression (RRR), and to assess their ability to predict all-cause mortality. Motivated by previous studies we chose percentages of energy from different macronutrients as response variables in the RRR analysis. We used data from 9356 German elderly subject enrolled in the European Prospective Investigation into Cancer and Nutrition study. The first RRR pattern, subjects which explained 30·8 % of variation in energy sources and especially much variation in intake of saturated fat, monounsaturated fat and carbohydrates was a significant predictor of all-cause mortality. The pattern score had high positive loadings in all types of meat, butter, sauces and eggs, and was inversely associated with bread and fruits. After adjustment for other known risk factors, the relative risks from the lowest to highest quintiles of the first RRR pattern score were 1·0, 1·01, 0·96, 1·32, 1·61 (P for trend: 0·0004). In contrast, the first two PCA patterns explaining 19·7 % of food intake variation but only 7·0 % of variation in energy sources were not related to mortality. These results suggest that variation in macronutrients is meaningful for mortality and that the RRR method is more appropriate than the classic PCA method to identify dietary patterns relevant to mortality.

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

Objective: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. Methods: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. Results: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. Conclusion: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation.

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north - south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival. © The Authors 2005.

Objective To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. Design Multicentre, prospective cohort study. Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. Results An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). Conclusion The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.

Background: In previous studies, dietary patterns were derived in different populations without regard to a specific outcome. Objective: The objective was to apply a new statistical method to construct a specific dietary pattern that is strongly associated with the risk of coronary artery disease (CAD). Design: We applied reduced rank regression to a sample of 200 cases and 255 controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study. The CAD-specific dietary pattern was constructed by choosing intake data for 49 food groups as predictors and 5 established biomarkers for CAD as responses. Results: A high score for the constructed dietary pattern was characterized by high intakes of meat, margarine, poultry, and sauce and low intakes of vegetarian dishes, wine, vegetables, and whole-grain cereals. After adjustment for known CAD risk factors, the relative risks from the lowest to the highest quintiles of the pattern score were 1.0, 1.1, 3.6, 6.2, and 12.3 (95% CI: 4.9, 30.9; P for trend 0.0001). There was an approximate 4.5-fold difference in C-reactive protein and a 2-fold difference in C-peptide between the highest and lowest score quintiles of the study population. HDL-cholesterol concentrations ranged from 70 mg/dL in the lowest quintile to 49 mg/dL in the highest quintile of dietary pattern score. Conclusion: The new statistical method, reduced rank regression, may be a useful tool for identifying dietary patterns that simultaneously affect the concentrations of known CAD biomarkers and the risk of developing CAD. Am J Clin Nutr 2004;80:633– 40.

Background/Aims: The role of dietary protein in bone health is controversial. The objective of the present study was to examine the association between protein intake, dietary calcium, and bone structure measured by broadband ultrasound attenuation (BUA). Methods: Our analysis includes 8,178 female study participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam Study. Ultrasound bone measurements were performed on the right os calcis, and BUA was determined. Dietary intake was assessed by a standardized food frequency questionnaire. We applied linear regression models to estimate the association between dietary protein and BUA. Results: After multivariate adjustment, high intake of animal protein was associated with decreased BUA values (β = –0.03; p = 0.010) whereas high vegetable protein intake was related to an increased BUA (β = 0.11; p = 0.007). The effect of dietary animal protein on BUA was modified by calcium intake. Conclusion: High consumption of protein from animal origin may be unfavourable, whereas a higher vegetable protein intake may be beneficial for bone health. Our results strengthen the hypothesis that high calcium intake combined with adequate protein intake based on a high ratio of vegetable to animal protein may be protective against osteoporosis.

Because foods are consumed in combination, it is difficult in observational studies to separate the effects of single foods on the development of diseases. A possible way to examine the combined effect of food intakes is to derive dietary patterns by using appropriate statistical methods. The objective of this study was to apply a new statistical method, reduced rank regression (RRR), that is more flexible and powerful than the classic principal component analysis. RRR can be used efficiently in nutritional epidemiology by choosing disease-specific response variables and determining combinations of food intake that explain as much response variation as possible. The authors applied RRR to extract dietary patterns from 49 food groups, specifying four diabetes-related nutrients and nutrient ratios as responses. Data were derived from a nested German case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam study consisting of 193 cases with incident type 2 diabetes identified until 2001 and 385 controls. The four factors extracted by RRR explained 93.1% of response variation, whereas the first four factors obtained by principal component analysis accounted for only 41.9%. In contrast to principal component analysis and other methods, the new RRR method extracted a significant risk factor for diabetes.

Objective:The World Health Organization (WHO) recommends a daily intake of at least 400?g of vegetables and fruit. The aim of this paper was to evaluate the public health benefit of meeting this WHO recommendation by applying a statistical method that combines estimated intake distributions and simulated intake changes.Design and setting:The benefit of an increased consumption of vegetables and fruit was quantified by the preventable proportion of diseases. This proportion was estimated by a general formula derived in the paper that incorporates individual relative risks. Three different strategies of increasing usual intake were simulated and compared. The first strategy assumes that all individuals increase their intake by the same amount, the second assumes a constant increase among low consumers, and the third simulates individual increments necessary to meet the WHO recommendation. Calculations were made for three different scenarios with varying relative risks.Results:The third simulation strategy turned out to be the most appropriate one to quantify the potential health gain of the current dietary recommendation. Applying this strategy to prevent cancer, the proportion of preventable cases was country-specific. Estimates for France and Sweden were 21.9% and 19.3%, respectively, which are somewhat lower than the non-specific figure published by the World Cancer Research Fund.Conclusions:To improve estimates of the preventable proportion of diseases, the estimation formula presented here can be applied. Its application requires intake data to estimate the initial intake distribution in the population and to simulate adequate dietary changes.

Exploratory factor analysis might work well in elucidating the major dietary patterns prevailing in specific study populations. However, patterns extracted in one study population and their associations with disease risk cannot be reproduced with this data-specific method in other study populations. To construct less population-dependent pattern variables of similar content as original exploratory patterns, we proposed to derive so-called simplified pattern variables. They represent the sum of the unweighted standardised food variables which loaded high at the pattern of interest. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study suggest that these simplified pattern variables might adequately approximate factor analysis-based dietary patterns. A simplified pattern variable based on the six highest loading food variables showed a correlation >0·95 with the originally derived factor score, which consisted of forty-seven food variables. Moreover, simplified pattern variables might adequately approximate patterns across different study populations. A simplified pattern variable showed similar factor loadings, ranging from 0·34 to 0·52, as well as similar associations with nutrient intake as a ‘western’ pattern originally reported from an US study population. These simplified pattern variables can subsequently be used to study pattern associations with disease risk, especially in multi-centre studies. It is therefore an approach that might overcome one of the most frequently claimed limitations of factor analyses applied in epidemiology: their non-comparable risk estimates.

A subclinical inflammatory reaction has been shown to precede the onset of type 2 (non-insulin-dependent) diabetes. We therefore examined prospectively the effects of the central inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) on the development of type 2 diabetes. We designed a nested case-control study within the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study including 27,548 individuals. Case subjects were defined to be those who were free of type 2 diabetes at baseline and subsequently developed type 2 diabetes during a 2.3-year follow-up period. A total of 192 cases of incident type 2 diabetes were identified and matched with 384 non-disease-developing control subjects. IL-6 and TNF-alpha levels were found to be elevated in participants with incident type 2 diabetes, whereas IL-1beta plasma levels did not differ between the groups. Analysis of single cytokines revealed IL-6 as an independent predictor of type 2 diabetes after adjustment for age, sex, BMI, waist-to-hip ratio (WHR), sports, smoking status, educational attainment, alcohol consumption, and HbA(1c) (4th vs. the 1st quartile: odds ratio [OR] 2.6, 95% CI 1.2-5.5). The association between TNF-alpha and future type 2 diabetes was no longer significant after adjustment for BMI or WHR. Interestingly, combined analysis of the cytokines revealed a significant interaction between IL-1beta and IL-6. In the fully adjusted model, participants with detectable levels of IL-1beta and elevated levels of IL-6 had an independently increased risk to develop type 2 diabetes (3.3, 1.7-6.8), whereas individuals with increased concentrations of IL-6 but undetectable levels of IL-1beta had no significantly increased risk, both compared with the low-level reference group. These results were confirmed in an analysis including only individuals with HbA(1c)5.8% at baseline. Our data suggest that the pattern of circulating inflammatory cytokines modifies the risk for type 2 diabetes. In particular, a combined elevation of IL-1beta and IL-6, rather than the isolated elevation of IL-6 alone, independently increases the risk of type 2 diabetes. These data strongly support the hypothesis that a subclinical inflammatory reaction has a role in the pathogenesis of type 2 diabetes.

Food-frequency questionnaire (FFQ) data should reflect interindividual variation and therefore measure variance in intake among populations. We conducted this analysis to evaluate the relevance of separate portion size questions to the interindividual variation in food intake. The contribution of portion size questions to the variance in food intake was quantified and compared with the variance when group-specific portion sizes would be assigned, using 26,764 FFQ of the European Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Groups were defined according to gender, age (50 y,/=50 y) or body mass index (BMI) (26 kg/m(2),/=26 kg/m(2)). The FFQ inquired about both consumption frequency and portion size. Linear regression models for each food item were fit with intake (g/d) as dependent variables and frequency of intake as independent variables. The mean coefficient of determination (R(2)) for the different food items explained by frequency only was 84.0% (71.2-95.7%). The R(2) for gender-, age- and BMI-specific frequencies of intake did not markedly alter the overall results. We conclude that the omission of individual portion size information would probably result in a notable reduction of interindividual variance. However, to reduce the respondents' burden and to increase data completeness in self-administration in large epidemiologic studies, the assignment of a constant portion size seems to be adequate. The variance was not increased markedly when constant gender-, age- and BMI-specific portion sizes were applied, thus supporting the assignment of an overall portion size.

Statistical analysis of pooled dietary intake data in multicenter and multiethnic studies is often hampered by lack of comparability due to application of different food frequency questionnaires (FFQs). To remove this deficiency, dietary intake measurements should be standardized. This paper presents a standardization procedure based on nonlinear calibration, which aims to approximate the usual intake distribution estimated by reference measurements. The method can be applied in studies with repeated standardized reference measurements that can refer to time periods different from that of the FFQ. It was developed especially for short-term reference assessment methods, such as 24-hour recalls, diet records, and biomarkers. Similar to linear calibration, the proposed method does not change the rankings of subjects in each center or group; therefore, it maintains the within-center validity of the FFQ data. In contrast to linear calibration, the mixture of nonlinearly calibrated intake measurements from different centers or groups corresponds to the mixture of usual intake expected from the reference measurements. This paper illustrates this property of achieving high between-center validity by using macronutrient intake data from the 1995-1996 European Prospective Investigation into Cancer and Nutrition-Potsdam validation study. Here, the proposed method is compared with three linear calibration methods.

Objective: To estimate the habitual dietary intake distribution in a population on the basis of repeated short-term measurements, especially of multiple 24 h diet recalls. Methods: Six different statistical methods were evaluated and compared. The comparison referred to theoretical assumptions, admitted data transformations, statistical foundations, available software packages, and applications to real data of dietary intake. Results: The Nusser method and a simplified version of it proposed in the paper have proved to be universally applicable methods for estimating the usual intake distribution for food groups and nutrients. Also, the Buck method seemed to be a robust estimation procedure suitable for the description of food consumption data, whereas the other considered methods were only applicable for log–normally distributed intake data or required a comprehensive data simulation. Characteristics of the estimated usual intake distribution were a decreased standard deviation, increased lower percentiles, and decreased upper percentiles compared to the observed sample distribution of individual means. Empirical results concerning total fat and vegetable intake in three different European consumption surveys showed that the estimated percentiles of the usual intake distribution did not depend markedly on the number of sampling days. Conclusions: Repeated short-term measurements like 24 h diet recalls can be used to describe the habitual dietary intake distribution in food consumption surveys. Recommended is a sampling design of two non-consecutive sampling days. The sampling days of all participants should be selected in such a way that they cover all seasons and days of the week. Sponsorship: European Commission, DG SANCO F/3, Health Monitoring.

This study examined the effect of food group intake on subsequent 2-y weight change. Food-frequency questionnaire-based food intake data of 17,369 nonsmoking subjects of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were examined in their relation to a subsequent weight change. Dietary data, collected from 1994 to 1998, were grouped into 24 food groups. Weight change per year follow-up was the outcome of interest; large weight gain was defined asor =2 kg; small weight gain asor =1 kg to2 kg; large weight loss asor = -2 kg; small weight loss asor = -1 kg to-2 kg and weight maintenance as +/- 1 kg. For each food group, a separate polytomous logistic regression model with stable weight as the reference group was constructed, controlling for age, body mass index, previous weight change, and behavioral and lifestyle factors. Odds ratios (OR) and 95% confidence intervals (CI) estimated the increase in risk associated with each 100 g/d increment in food group intake. In women, consumption of high energy, high fat food groups significantly predicted large weight gain, e.g., fats (OR = 1.75; 95% CI, 1.01-3.06), sauces (OR = 2.12; 95% CI, 1.17-3.82) and meat (OR = 1.36; 95% CI, 1.04-1.79), and the consumption of cereals predicted large weight loss (OR = 1.43; 95% CI, 1.09-1.88). In men, intake of high energy, high sugar foods, i.e., sweets, was significantly predictive of large weight gain (OR = 1.48; 95% CI, 1.03-2.13). Our data show that a diet rich in high fat and high energy foods predicts short-term weight gain even if controlled for many potential confounding factors.

Objective: Gynaecologic surgeries and hormone medication increasingly interfere with the concept of determining menopausal status based on self-reported data about the last menstrual period—an approach frequently applied in epidemiological studies. This analysis compared different approaches of menopausal status determination, including a probabilistic approach that was developed to reduce misclassification of menopausal status. Methods: Interview and questionnaire data relating to hormone status from about 16 000 German women were used to determine menopausal status using different approaches: menses based, age based, self-assessment based, and a probabilistic approach. Results: Applying strict menses-based criteria, 29.1% of the women were found to be with undetermined menopausal status. The probabilistic approach was applied to determine menopausal status and age at menopause for these women. The proposed approach uses the current age of the women with undetermined menopausal status, and the relative age-dependent frequencies of pre- or postmenopausal status among those with natural menopausal status to calculate weighting factors, which represent the probabilities of being pre- and postmenopausal of each woman previously undetermined. Correspondingly, the missing age at menopause was estimated with the same probabilistic approach. Applying various approaches to determine menopausal status, the ratio of pre- to postmenopausal women differed considerably, ranging from 1.03 to 1.61. In addition, considerable differences were observed with respect to the number of missing values for both menopausal status and age at menopause. Conclusion: The probabilistic approach allowed to estimate menopausal status and age at menopause with the advantage that all available information from the entire study population and from the individual is used.

As part of the representative Environmental Survey in Germany in 1990-1992, investigators determined cadmium levels in blood provided by 3,965 subjects aged 25-69 yr. The investigators considered approximately 150 variables (i.e., demographics, household and occupational characteristics, environmental exposures, smoking habits, frequency of food consumption, and additional life-style features) as potential predictors in multivariate regression analysis. On the basis of the results of multivariate regression analysis, the authors derived 2 slightly different models for the prediction of blood cadmium levels in populations from West and East Germany. Both models included 3 primary predictors of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed variance in blood cadmium levels in West and East Germany, respectively. The most important predictor was a specific indicator for smoking habits, which was determined from a separate mathematical model. In this model, the effect of smoking was considered, and the model accounted for the biological half-life of cadmium in blood.

Under-reporting of alcohol intake has been frequently reported. However, due to the lack of an objective reference method, e.g. a biomarker, information about the extent of under-reporting of alcohol intake obtained with dietary assessment instruments is not available. The objective of this study was to compare reported alcohol intake data derived from a 24 h recall with a biomarker of recent alcohol intake, the urinary excretion of 5-hydroxytryptophol (5-HTOL):5-hydroxyindole-3-acetic acid (5-HIAA). Embedded into the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, Germany, a validation study that collected 24 h recall data and 24 h urine samples was conducted. Cohort study participants (n107) volunteered to participate in this validation study. Among them were five subjects who reported no consumption of alcoholic beverages but had a 5-HTOL:5-HIAA ratio that indicated recent alcohol intake when the clinical cut-off point was taken as a judging criterion. After exclusion of these under-reporters, the Pearson's correlation coefficient between reported alcohol intake and the 5-HTOL:5-HIAA ratio was 0.92 (P